Fluoroquinolones (FQs) are life-saving drugs and the most widely prescribed antibiotics to adults in the United States. Unfortunately, it is now well-established that bacterial resistance to FQs is significant, and resistance has been established to the point that these drugs are no longer useful for some of the most serious infections. For example, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) harbor a key mutation in their DNA gyrase that render them insensitive to FQs. This mutation of a serine in the GyrA subunit near the enzyme active site is observed in close to 100% of MRSA and VRE. Thus there is a critical need for the discovery and development of novel compounds that are active against pathogenic bacteria, including bacteria possessing fluoroquinolone resistance (FQR). This need is already acute for MRSA and VRE, and will also become urgent for other pathogens as FQ-resistance continues to rise.